Transcranial magnetic stimulation system and methods

ABSTRACT

A system and methods for transcranial magnetic stimulation, the system including a helmet, a positioning portion, a stimulator and a cooling system, are disclosed. The helmet includes a coil for deep brain magnetic stimulation. The coil has a base portion, and return portions, which may include a protruding return portion and a contacting return portion. The coil is designed to minimize unintended stimulation of portions of the brain, while reducing accumulation of surface charges. The coil is stimulated at several locations and/or at different times so as to focus the electrical field on a specific deep neuronal structure.

FIELD OF THE INVENTION

The present invention relates to a system and methods for deeptranscranial magnetic stimulation, and more particularly, to an improvedsystem and method for stimulating specific regions of the brain whileminimizing pain and side effects.

BACKGROUND OF THE INVENTION

Transcranial magnetic stimulation (TMS) is widely used as a researchtool to study aspects of the human brain and has recently been used as atool in therapeutic neuropsychiatry.

Biological tissue can be stimulated using magnetic fields produced bypassing electrical currents through electrically conductive materialspositioned adjacent to the tissue. The magnetic fields are intended toinduce an electric field in a tissue, provided that the tissue is aconductive medium. More specifically, magnetic stimulation can causeelectric conduction in brain cells, and, as a consequence, generation ofaction potentials.

The magnetic stimulation is delivered or generated by a coil, positionedon the patient's scalp, inducing nerve stimulation within the brain.Current magnetic stimulation techniques and coils are suitable forsuperficial stimulation of brain, whereas for some medical indications,deeper stimulation would be essential. As superficial stimulation doesnot induce effective stimulation in the prefrontal cortex (which lays3-4 cm in depth) and other reward and mood-related brain structures suchas the nucleus accumbens (ventral striatum), it may be predicted thatdeeper brain stimulation may be more effective for the treatment ofmajor depression and other psychiatric and neurological disorders suchas autism, post-traumatic stress disorder (PTSD), addictive behaviorsincluding smoking, overeating and drug addiction, schizophrenia,Parkinson's disease, and others. Stimulation of deep brain regionsrequires a very high intensity which cannot be reached by the magneticstimulators available today, using standard circular, figure-eight orDouble Cone coils without causing undesirable side effects, such as, forexample, epileptic seizures or other problems associated withover-stimulation of cortical regions.

A novel approach to TMS has been previously described in InternationalPublication Number WO 02/32504, wherein deep brain stimulation is madepossible while minimizing side effects. The device described thereinincludes a base and an extension portion, the base having individualwindings for individual paths of current flow, and the extension portiondesigned so as to minimize unwanted stimulation of other regions of thebrain.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided acoil for magnetic stimulation of a target area, wherein the coil ispositionable on a body part. The coil includes a base portion, aprotruding return portion, and a contacting return portion. The baseportion includes at least one member for providing electrical currentflow in a direction tangential to the target area, and is positioned ata first level with respect to the target area. The protruding returnportion is configured for carrying returning current in a directionopposite the target area, is in electrical communication with the atleast one member of the base portion, and is positioned at a secondlevel with respect to the target area, the second level located at adistance above the first level. The contacting return portion isconfigured for carrying returning current in a direction opposite thetarget area, is in electrical communication with the at least one memberof the base portion, and is positioned substantially in the first leveland spaced at a distance from the target area.

According to further features in preferred embodiments of the inventiondescribed below, the at least one member can include multiple members,and in specific preferred embodiments can include 10 or 14 members. In apreferred embodiment, a portion of the multiple members is in electricalcommunication with the protruding return portion and a portion of themultiple members is in electrical communication with the contactingreturn portion. Members are positioned in a lateral-medial direction oran anterior-posterior direction, or both, and are preferably parallel toone another.

According to further features in preferred embodiments of the inventiondescribed below, the first level is on the skull, and the distance ofthe second level above the first level is approximately 4-10 cm andpreferably around 7 cm. The distance of the contacting return portionfrom the target area is approximately 7-10 cm.

According to further features in preferred embodiments of the inventiondescribed below, the base portion has an arch configuration which iscomplementary to the body part. In a preferred embodiment, the body partis the head and the target area is a portion of the brain, wherein thebase portion is configured to fit onto the head or skull of a subject.In a preferred embodiment, the portion of the brain is a deep area, andis at least 3 cm deep.

According to another aspect of the present invention there is provided asystem for transcranial magnetic stimulation. The system includes ahelmet for placement on a head of a subject, a positioning portion, astimulator and a cooling system. The helmet includes at least one coilfor magnetic stimulation, a rigid cover portion, and a flexible coverportion. The positioning portion includes a stand and an adjustable armattached to the rigid cover portion of the helmet. The stimulator is inelectrical communication with the coil. The cooling system includes anexternal unit and an internal system, wherein the internal system is inthermal proximity and approximate geometric alignment with at least aportion of the coil.

According to further features in preferred embodiments of the inventiondescribed below, the positionable portion further includes a chair and arear head support. The system may further include an additionalstimulator, in electrical communication with the coil. In preferredembodiments, the internal system is a radiator system which is separatedfrom the coil by an insulator, such as a polyurethane resin.

According to another aspect of the present invention there is provided amethod for stimulation of a deep brain region. The method includesproviding a coil in accordance with preferred embodiments of the presentinvention described herein, placing the coil on the skull of a subject,such that a base portion and a contacting return portion are in contactwith the skull and a protruding return portion is located at a distanceabove the skull, and activating the coil to stimulate the deep brainregion.

According to further features in preferred embodiments of the inventiondescribed below, the activating includes providing electrical impulsesto the coils. This can be done simultaneously, sequentially, or in arandom sequence.

According to yet another aspect of the present invention there isprovided a method of activating a neuronal structure. The methodincludes providing a coil for delivery of electrical impulses to atarget area, the coil including individual members designed to carrycurrent in predetermined directions, and activating the individualmembers non-simultaneously.

According to further features in preferred embodiments of the inventiondescribed below, the predetermined directions are the same direction foreach of the individual members. Alternatively, the predetermineddirections are a different direction for each of the individual members,and each of the predetermined directions forms a path designed to mimica neuronal structure. In some embodiments, the activating includessequentially activating each of the individual members, while in otherembodiments, the activating includes randomly activating each of theindividual members or selectively activating only some of the individualmembers.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1A is a schematic illustration of a system in accordance with apreferred embodiment of the present invention;

FIG. 1B is an illustration of a helmet from the system of FIG. 1A;

FIG. 2A is an illustration of a prior art device including a frame andan electrically conductive coil having a base and an outwardlyprojecting extension portion;

FIG. 2B is a schematic diagram illustrating conducting wires and currentflow in the prior art embodiment illustrated in FIG. 2A;

FIG. 3A is an illustration of a prior art device including a frame andan electrically conductive coil having a base and an outwardlyprojecting extension portion with a plurality of radially elongatedextension elements;

FIG. 3B is a schematic diagram illustrating conducting wires and currentflow in the prior art embodiment illustrated in FIG. 3A;

FIG. 4 is an illustration of a coil for TMS in accordance with onepreferred embodiment of the present invention;

FIG. 5 is an illustration of a coil for TMS in accordance with anotherpreferred embodiment of the present invention;

FIG. 6 is a block diagram illustration of a cooling system in accordancewith a preferred embodiment of the present invention;

FIG. 7 is a block diagram illustration of external cooling unit from thecooling system depicted in FIG. 6;

FIG. 8 is a block diagram illustration of a liquid circulator from thecooling system depicted in FIG. 6;

FIG. 9 is a schematic illustration of an internal system in contact withcoils illustrated in FIGS. 4 and 5, in accordance with one preferredembodiment of the present invention;

FIG. 10 is a graphical illustration of a strength/duration curve foractivation of an action potential;

FIG. 11 is an illustration of a coil designed to stimulate the rightabductor pollicis brevis in an experimental trial on humans; and

FIG. 12 is a graphical illustration of the results of performingstimulation using the coil of FIG. 11 as compared to a standard figure-8coil.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a method for stimulating deep brain regionsusing TMS. Specifically, the present invention can be used to stimulatedeep regions of the brain while maintaining a high percentage of fieldintensity as compared to superficial regions.

The principles and operation of a system and methods for transcranialmagnetic stimulation according to the present invention may be betterunderstood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Reference is now made to FIG. 1A, which is a schematic illustration of asystem 80 in accordance with a preferred embodiment of the presentinvention. System 80 includes a helmet 82 which holds coils for magneticstimulation and is positionable around a head of a subject. Helmet 82 isadjustable via positioning portion 84. Positioning portion includes astand 81 with an adjustable arm 83, a chair 85 with a rear head support87, and an adaptor 89 between helmet 82 and adjustable arm 83. Astimulator 86 is in electrical communication with the coils of helmet82, and is designed to provide electrical stimulation to the coils.Stimulator 86 is a commercially available neurostimulator, such as anyof the various models of magnetic stimulators produced by Medtronic,Inc. of Minneapolis, Minn., USA (e.g., MagPro, MagLite Compact), orpower supplies sold with various models of magnetic stimulators producedby Magstim Company US, LLC, of New York, N.Y., USA (e.g., Magstim Model200, Magstim Model 220, Magstim Model 250, BiStim, Magstim Rapid,Magstim QuadroPulse). Stimulator 86 is used to deliver electricalstimulation to the brain, and provides a controlled output, frequency,and pulse duration, and may also include an indication of coiltemperature. A cooling system 88 is also in communication with the coilsof helmet 82, and is designed to maintain an ambient temperature in thecoils during repetitive stimulation provided by stimulator 86. Coolingsystem 88 may be a system based on air cooling using a Freon system, ora thermoelectric cooler (TEC) system such as the TECs produced by MelcorLtd, (Trenton, N.J., USA), with either open air pathways or closed,two-direction air pathways, or cooling system 88 may be a liquid coolingsystem. A particular example of a cooling system 88, designedspecifically for use with the coils of the present invention, will bedescribed in further detail herein below with respect to FIGS. 6-9.

Reference is now made to FIG. 1B, which is a more detailed schematicillustration of helmet 82 in accordance with a preferred embodiment ofthe present invention. Helmet 82 includes a rigid cover 90 and aflexible cover 92. Flexible cover 92 is designed to provide flexibilityover the head. An internal wall of helmet 82 is lined with a sponge forpadding. In one embodiment, the liner is a 0.9 mm biocompatible spongewith one-sided glue (3M Foam Medical Tape). Adaptor 89 is attached to anupper portion of stand 81 via an adjustment screw 94. Adjustment screw94 enables adjustment of the height or angle of helmet 82. Wires 96, 98run from stimulator 86 and cooling system 88 to helmet 82.

Positioned within helmet 82 are coils for transcranial magneticstimulation. Coils are designed to penetrate deep regions of the brain,while minimizing adverse side effects. The basic principles of operationof coils suitable for deep brain stimulation are as follows:

1. Proper Orientation of Stimulating Coils.

Coils must be oriented such that they will produce a considerable fieldin a direction tangential to the surface, which should also be thepreferable direction to activate the neurons under consideration. Thatis, wires of the coils are directed in one or more directions, whichresults in a preferred activation of neuronal structures orientated inthese particular directions. In some cases, there is one preferreddirection along the length or width axis, and in other cases, there aretwo preferred directions along both the length and width axes. Thus, theplacement and orientation of activating coils on the skull is important.

2. Minimization of Non-tangential Coil Elements.

Electrical field intensity in the tissue to be stimulated and the rateof decrease of electrical field as a function of distance from the coildepend on the orientation of the coil elements relative to the tissuesurface. It has been shown that coil elements which are perpendicular tothe surface induce accumulation of surface charge, which leads tocancellation of the perpendicular component of the induced field at allpoints within the tissue, and reduction of the electrical field in allother directions. Thus, the length of coil elements which are nottangential to the brain tissue surface should be minimized. Furthermore,the non-tangential coil elements should be as small as possible andplaced as far as possible from the deep region to be activated. Thecombination of these two factors helps to minimize accumulation ofsurface charge.

3. Maximization of the Field in the Deep Region as Compared with theField at the Cortex.

A major goal of deep TMS is to maximize deep region stimulation withoutcausing a large electrical field at surface areas of the brain. If theelectrical field at the surface areas is too large, it can cause pain,epileptic seizures, or other complications. Thus, it is important to tryto maximize deep region stimulation without causing a large electricalfield to accumulate at surface areas. This can be accomplished bysummation of electrical impulses, a concept which will be describedfurther hereinbelow. In addition the coil elements leading currents in adirection opposite to the preferred direction (the return paths), shouldbe located far from the desired brain region.

For purposes of better understanding the present invention, asillustrated in FIGS. 4-10 of the drawings, reference is first made tothe construction and operation of prior art coils as illustrated inFIGS. 2A, 2B, 3A and 3B. The coils are shown in two different, whichhave been previously disclosed in International Publication Number WO02/32504, entitled, “Coil for magnetic stimulation and methods for usingthe same,” incorporated by reference herein in its entirety.

Referring now to FIG. 2A, a device 11 includes a frame and anelectrically conductive coil having a base 12 and an outwardlyprojecting extension portion 14. In some embodiments, the frame itselfis the electrically conductive coil, such as a frame composed ofelectrically conductive material. In other embodiments, however, theframe is a flexible or malleable material, which may be configured to adesired shape for a specific application, and the electricallyconductive coil comprises one or more windings of electricallyconductive material associated with the frame, such as being runalongside of, mounted to, wound around, or placed inside the frame. Thebase 12 has a concave first side 19, which is directed toward the bodypart of the subject, and a second side 20 opposite first side 19. Theextension portion 14 extends outwardly from this second side and awayfrom the base.

Device 11 can be placed in various orientations around the skull.However, device 11 effectively induces electric fields within the bodyof a subject when the device 11 is placed with the concave side 19 ofthe base 12 facing the body of the subject.

The device 11 pictured in FIG. 2A has a partially toroidal or ovate base12 with a first end 22 and a second end 24. A line extending betweenthese two ends 22, 24 defines a length axis along the length of the base12. The base 12 has a substantially arcuate, semi-circular or semi-ovateshape along its length axis. The base 12 also has a width axis extendingperpendicular to its length axis and this width axis has a substantiallyarcuate, semi-circular or semi-ovate shape. Thus, the base 12 picturedin FIG. 2A comprises an arch extending along its length axis and an archextending along its width axis. The arch configurations along both thelength and width axes are complementary to the external shape of thebody part with which the device is to be used. The device conforms tothe side-to-side and front-to-back arch shape of a subject's skull.

As shown in FIG. 2A, the base 12 includes a pair of substantiallyparallel, arcuate, elongate, longitudinally-extending, laterally spacedframe members 21 and 23. Extending between and interconnectinglongitudinal frame members 21 and 23 are ten elongate, arcuate,transverse frame members 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Members 1-10 arespaced apart along the lengths of longitudinal frame members 21 and 23and are coupled at their opposite ends to, and extend generally at rightangles to, longitudinal frame members 21 and 23.

The extension 14 provides a path for the flow of electricity to and fromthe base 12. A surface charge can interfere with and reduce the strengthof the electric field produced by the coil portions in the base.Reduction in surface charge is accomplished by using a triangular, orupwardly converging, extension 14. The extension 14 comprises first andsecond elongated elements 26, 28. The elements have a first set of innerends 30, 32 connected to the base 12 at positions spaced apart along thelength of the axis of the base 12. The first elongated element 26 has afirst inner end 30 connected to the base 12 adjacent to the first end 22of the base 12, and the second elongated element 28 has a first innerend 32 connected to the base 12 adjacent to the second end 24 of thebase 12. The remainder portions 34, 36 of these elements 26, 28 extendaway from the base 12 and converge toward each other.

FIG. 2B is a schematic diagram illustrating conducting wires and currentflow in the embodiment illustrated in FIG. 2A. In FIG. 2B, pointslabeled A-J and AA-JJ are associated with the base, and points Q-V areassociated with the extension portion. Points U and V correspond to theelectrical inputs for the current produced by the power supply (notshown). Using the diagram of FIG. 2B as a guide, one can understand howa coil might be constructed for the embodiment of FIG. 2A. For example,the device 11 illustrated by FIG. 2A could comprise a coil having tenwindings numbered 1-10 extending in the arch width direction of the basealong the ten elongate, arcuate transverse frame members 1-10. Table 1summarizes such a placement of windings. TABLE 1 Winding No. Pathway 1V-R-H-I-J-JJ-II-HH-Q-U 2 V-R-H-I-II-HH-Q-U 3 V-R-H-HH-Q-U 4V-R-F-G-GG-FF-Q-U 5 V-R-F-FF-Q-U 6 V-T-E-EE-S-U 7 V-T-E-D-DD-EE-S-U 8V-T-C-CC-S-U 9 V-T-C-B-BB-CC-S-U 10 V-T-C-B-A-AA-BB-CC-S-U

A significant portion of the current flowing through the base flowsthrough the transverse strips of the coil and therefore, is orientedsubstantially along the reference z-axis shown in FIG. 2A. The coilportions associated with the base are complementary and tangential tothe surface of the subject's skull. In particular embodiments, the totallength of the coil associated with the transverse frame elements 1-10(i.e. substantially parallel to the width axis of the base) exceeds theremaining length of the coil associated with the base (i.e. theremaining length substantially parallel to the length axis of the base).In these embodiments, a majority of the current flowing through the baseis oriented substantially along the referenced z-axis shown in FIG. 2A.

An alternative embodiment of the device disclosed in InternationalPublication Number WO 02/32504 is depicted in FIGS. 3A and 3B. A device11A has a base 12A and an extension portion 14A, where base 12A has afirst end 22A and a second end 24A, and a substantially arcuate,semi-circular or semi-ovate shape along its length and width axes.However, in this embodiment, extension 14A includes a plurality ofradially elongated extension elements 110, 112, 114, . . . 158, 160,rather than a minimal number of radially elongated elements 26, 28 shownin FIG. 2A. The embodiment shown in FIG. 3A includes twenty-six radiallyextending elongated extension elements 110, 112, 114, . . . 158, 160,although alternative embodiments may employ a different number of suchelongated extension elements. As illustrated, the radially elongatedelements 110, 112, 114, . . . 158, 160 are collected into four fan-likegroupings 170, 172, 174, 176, and elongated elements 134 and 136 areconnected by lateral elements 180 and 182.

Similar to base 12 illustrated in FIG. 2A, base 12A illustrated in FIG.3A includes a pair of substantially parallel, arcuate, elongate,longitudinally-extending, laterally spaced frame members 21A and 23A.Extending between and interconnecting longitudinal frame members 21A and23A are twenty-six elongate, arcuate transverse frame members 210, 212,214, . . . 258, 260.

The amount of surface charge, and the influence of that surface chargeon the deeper tissues of the subject's body that are stimulated, dependson the overall lengths and locations of the electrical components whichcontain non-tangential components. In this embodiment, the overalllengths of such non-tangential elements are reduced and their distancesfrom the deep brain regions aimed for activation are increased. In otherwords, the ratio of the total length of the coil extending radially fromthe base to the total length of the coil associated with the base isless than the corresponding ratio in the previous embodiment, shown inFIG. 2A.

FIG. 3B is a schematic illustration of current flow through the windingsof the embodiment illustrated in FIG. 3A, with reference numeralscorrelating these windings to certain structures illustrated in FIG. 3A.FIG. 3B is not a circuit diagram in the true sense—this illustrationsimply shows how a coil for the device may be made from individualwindings of the coil, with each individual winding comprising a circuit.For the sake of clarity, only part of the entire device is shown.

As illustrated in FIG. 3B, the direction of electrical current flow isthe same in all of the twenty-six strips of the base 12A, flowing in adirection from the lateral frame member 23A to lateral frame member 21A.Generally, current to this portion of the coil arrives at Z, travelsdown to I₂, and flows through strips J₂-J₁, K₂-K₁, L₂-L₁, and M₂-M₁.Each strip (A₂-A₁, B₂-B₁, . . . M₂-M₁) has a return path through anelongated element 110, 112, 114, . . . 158, 160 of one of the fan-likegroupings 170, 172, 174, 176. For example, the return path for stripJ₂-J₁ may be elongated element 140 (not shown in FIG. 3B). The currentflows to I₂ then flows through strip H₂-H₁, and to I₁. From here, thecurrent flows up the extension to W, then to X (the line W-Xrepresenting the junction of two elongated elements 148 and 150), thento G₂, then through strips F₂-F₁, E₂-E₁, D₂-D₁, C₂-C₁, B₂-B₁, A₂-A₁, andreturns to G₂. Each of strips F₂-F₁, E₂-E₁, D₂-D₁, C₂-C₁, B₂-B₁, A₂-A₁,has a return path through an elongated element of fan-like collection176 composed of elongated elements 150-160. The return paths of currentflow are in the opposite directions of the strips. As in the firstembodiment, shown in FIG. 2A, extension portion 14A of this secondembodiment places electrical currents flowing through the return pathsaway from the subject, to reduce their electrical effect on the bodytissues of the subject.

In the two prior art embodiments of a device for magnetic stimulationdescribed above with reference to FIGS. 2A-B and 3A-B, return paths areplaced away from the subject, to reduce their electrical effect on thebody tissues of the subject. However, increasing the distance from theskull requires longer non-tangential elements and causes an accumulationof surface charges, which increases the decay in electrical field withdepth. These conflicting principles are balanced as much as possible, soas to minimize both unwanted electrical effects due to current flow inthe return paths and unwanted accumulation of surface charges.

In the present invention, a design to further decrease the lengths ofnon-tangential elements (and thus minimize unwanted surface charges atthe area of stimulation) is described. The embodiments described hereinare particularly useful in cases where the region to be stimulated isnot on a central line of the brain, such as prefrontal regions.

Reference is now made to FIG. 4, which is an illustration of a coil 300for TMS in accordance with one preferred embodiment of the presentinvention. Coil 300 includes a base portion 312, a protruding returnportion 314, and a contacting return portion 315. Base portion 312 iscomprised of windings 317 of electrically conductive material. Baseportion 312 has a concave first side 319, which is in direct contactwith the skull and is directed toward the body part of the subject, anda second side 320 opposite first side 319. Protruding return portion 314extends outwardly from second side 320 and away from base portion 312,and contacting return portion 315 is positioned a distance from baseportion 312, but is in contact with the skull. Thus, base portion 312can be considered to be at a first level with respect to the targetarea. Protruding return portion 314 is at a second level which is at adistance from the first level in the y-direction. Contacting returnportion 315 is at the first level, that is, is approximately on the sameplane as base portion 312, but is at a planar distance (in the x-zplane) from the target area. Windings 317 are designed to be in contactwith the skull, and may either be pre-formed or malleable to accommodatethe curved anatomy of the area on which it is to be placed. This designmaximizes tangential stimulation, which is optimal for axonaldepolarization.

The device 300 pictured in FIG. 4 has an arcuate base 312 with a firstend 322 and a second end 324. A line extending between these two ends322, 324 defines a length axis along the length of the base 312. Thebase 312 has a substantially arcuate, semi-circular or semi-ovate shapealong its length axis. The base 312 also has a width axis extendingperpendicular to its length axis and this width axis has substantiallyarcuate, semi-circular or semi-ovate shape. Thus, the base 312 picturedin FIG. 4 comprises an arch extending along its length axis and an archextending along its width axis. The arch configurations along both thelength and width axes are complementary to the external shape of thebody part with which the device is to be used. The device conforms tothe side-to-side and front-to-back arch shape of a subject's skull.

Base 312 includes windings 317, which are comprised of a series ofsubstantially parallel members 301-310. In the embodiment depicted inFIG. 4, members 301-310 are oriented in a lateral-medial direction,making device 300 suitable for activating structures in the prefrontalcortex and fibers connecting the cingulate or prefrontal cortex with thenucleus accumbens and ventral tegmental area. These are neuronalpathways related to the control of motivation, reward and pleasure. Eachof members 301-310 carries an electrical current in the lateral-medialdirection (substantially parallel with the length axis of base 312),with the direction of the current being the same in each of members301-310. Each of members 301-310 has a return path, extending througheither protruding return portion 314 or through contacting returnportion 315. The members 301-310 are electrically connected to a powersupply, such as by electrical leads 316, 318. In a preferred embodiment,each of members 301-310 is 14-22 cm in length. In one embodiment, thereis a separation of 0.5-1.5 cm between each of members 301-310. In apreferred embodiment, there is a separation of 0.8 cm between each ofmembers 301-310. The return paths 306″-310″ of members 306-310 aresituated above the head at a distance therefrom as delineated bysegments H-I. In one embodiment, the distance from the head to thereturn paths 306″-3 10″ of members 306-310 is between 4-10 cm. In apreferred embodiment, the distance from the head to the return paths306″-310″ of members 306-310 is approximately 7 cm.

Coil 300 may be composed of any electrically conductive material, suchas metal. Particular embodiments have coils comprising wire made ofcopper, aluminum, or other electrically conductive material. In apreferred embodiment, the coil is made of a double 14 AWG insulatedcopper wire having a total length of 800 cm and winded into windings317, connected in series. In another embodiment the coil is made from amultiline wire composed of 40-60 lines of 3 mm cross section. In apreferred embodiment, coil elements are coated by a polyurethane resintype Resinex 4 (Hamchaber Veharikasher Ltd., Israel), for additionalelectrical insulation. In alternative embodiments, coil elements arecoated by other insulating materials, such as PVC, or are sandwichedbetween layers of insulating materials. It should be readily apparentthat the embodiments disclosed herein are examples only and should notbe regarded as limiting. The windings 317 are connected to anappropriate cable and connector, which is then connected to astimulator. The stimulator may be any appropriate commercially availablepower supply, such as the power supplies available for use with othermagnetic coils. In preferred embodiments, the stimulator is one ofvarious models of magnetic stimulators produced by Medtronic, Inc. ofMinneapolis, Minn., USA (e.g., MagPro, MagLite Compact), or powersupplies sold with various models of magnetic stimulators produced byMagstim Company US, LLC, of New York, N.Y., USA (e.g., Magstim Model200, Magstim Model 220, Magstim Model 250, BiStim, Magstim Rapid,Magstim QuadroPulse).

A power supply or stimulator (not shown) supplies current through lead316 into one of members 301-310. The stimulating current pulses flowsubstantially in the lateral-medial direction. Current then ascendsthrough an ascending portion 311 extending upwards from base portion312. At this point, current can take one of two paths—either throughprotruding return portion 314 or through contacting return portion 315.If current runs through protruding return portion 314, it runs fromascending portion 311, through protruding return portion (which runssubstantially parallel to members of base portion 312), and back down tothe level of the skull at a descending portion 323. From there, currentreturns through lead 318 back into the power supply. If current runsthrough contacting return portion 315, it runs from ascending portion311, to a descending connector 313, through contacting return portion315 (which runs substantially parallel to members of base portion 312and is positioned directly on the skull, but at a distance from members301-310 of base portion 312), to an ascending connector 321, and backdown to the level of the skull at descending portion 323. From there,current returns through lead 318 back into the power supply. In apreferred embodiment, half of the members run through protruding returnportion 315 and half of them run through contacting return portion 314.However, the invention is not limited to this proportion, and anyproportion of protruding return paths and contacting return paths ispossible, so long as each return path receives current from at least oneof the members. Current may be supplied simultaneously to all members,or alternatively, may be supplied sequentially, in a random order, orselectively. In another embodiment, current is supplied to member 301,and runs through a loop including each of the additional members301-310. It should also be readily apparent that although the inventionhas been shown with reference to ten members, the invention is not inany way limited to this number, and any suitable number of members maybe used. In additional embodiments, a single member may have a returnpath through both protruding return portion 314 and contacting returnportion 315.

In the preferred embodiment depicted in FIG. 4, current from each ofmembers 301-310 runs through ascending portion 311 via pathways301′-310′. At the top of ascending portion 311, current from members301-305 runs through contacting return portion 315 via pathways301″-305″ while current from members 306-310 runs through protrudingreturn portion 314 via pathways 306″-310″. Specifically, members 301-303traverse the path A-B-C-D-E-F-G-H-I-J-Q-R-S-T-K-L-A. Member 304traverses the path A-B-G-H-I-J-Q-R-S-T-K-L-A. Member 305 traverses thepath A-M-N-B-G-O-P-H-I-J-Q-R-S-T-K-L-A. Members 306-307 traverse thepath A-M-N-B-G-O-P-H-I-J-K-L-A. Members 308-309 traverse the pathA-B-G-H-I-J-K-L-A. Member 310 traverses the path A-H-I-J-K-L-A. Itshould be readily apparent that other combinations and pathways arepossible, and are within the scope of the present invention.

Protruding return portion 314 is spaced a distance from the skull, asdescribed above. By placing the return path at a distance from theskull, electrical stimulation of unwanted portions of the brain isminimized. However, surface charge accumulation at the surface of thebrain is increased. As such, some of the return paths are placed on theskull itself, so as to reduce surface charge accumulation. However,these return paths are placed a distance from the site to be stimulatedwithin the brain so as to avoid conflicting signals in the area ofstimulation. In a preferred embodiment, the distance from the members tothe contacting return paths is at least 5 cm. In some embodiments, thedistance from the members to the contacting return paths is in the rangeof 7-20 cm. In a preferred embodiment, the distance is approximately 10cm. Thus, a balance is maintained between the need for reducing surfacecharge and the conflicting need to avoid electrical stimulation ofunwanted portions of the brain.

Reference is now made to FIG. 5, which is an illustration of a coil 400for TMS in accordance with another preferred embodiment of the presentinvention. In this embodiment, members 401-414 are oriented in ananterior-posterior direction, for activation of structures in theprefrontal cortex and fibers connecting the cingulate or prefrontalcortex with the nucleus accumbens and ventral tegmental area, withpreference for the left hemisphere These are neuronal pathways relatedto the control of motivation, reward and pleasure. Coil 400 includes abase portion 425, a protruding return portion 440, and a contactingreturn portion 415. Base portion 425 is comprised of windings 417 ofelectrically conductive material. Base portion 425 has a concave first,or inner side 419, which is in direct contact with the skull and isdirected toward the body part of the subject, and a second, or outerside 420 opposite first side 419. Protruding return portion 440 extendsoutwardly from second side 420 and away from base portion 425, andcontacting return portion 415 is positioned a distance from base portion425, but is in contact with the skull. Thus, base portion 425 can beconsidered to be at a first level with respect to the target area.Protruding return portion 440 is at a second level which is at adistance from the first level in the y-direction. Contacting returnportion 415 is at the first level, that is, is approximately on the sameplane as base portion 425, but is at a planar distance (in the x-zplane) from the target area. Windings 417 are designed to be in contactwith the skull, and may either be pre-formed or malleable to accommodatethe curved anatomy of the area on which it is to be placed. This designmaximizes tangential stimulation, which is optimal for axonaldepolarization.

The device 400 pictured in FIG. 5 has an arcuate base 425 with a firstend 422 and a second end 424. A line extending between these two ends422, 424 defines a length axis along the length of the base 425. Thebase 425 has a substantially arcuate, semi-circular or semi-ovate shapealong its length axis. The base 425 also has a width axis extendingperpendicular to its length axis and this width axis has substantiallyarcuate, semi-circular or semi-ovate shape. Thus, the base 425 picturedin FIG. 5 comprises an arch extending along its length axis and an archextending along its width axis. The arch configurations along both thelength and width axes are complementary to the external shape of thebody part with which the device is to be used. The device conforms tothe side-to-side and front-to-back arch shape of a subject's skull.

Base 425 includes windings 417, which are comprised of a series ofsubstantially parallel members 401-414. In the embodiment depicted inFIG. 5, members 401-414 are oriented in an anterior-posterior direction,making device 400 suitable for activating structures in the prefrontalcortex. Each of members 401-414 carries an electrical current in theanterior-posterior direction (substantially perpendicular with thelength axis of base 425), with the direction of the current being thesame in each of members 401-414. Each of members 401-414 has a returnpath, extending through either protruding return portion 440 or throughcontacting return portion 415. The members 401-414 are electricallyconnected to a power supply, such as by electrical leads 416, 418. In apreferred embodiment, each of members 401-414 has a length of 7-12 cm.The 14 members 401-414 are distributed above the prefrontal cortex ofthe left hemisphere. In one embodiment, there is a separation of 0.5-1.5cm between each of members 401-414. In a preferred embodiment, there isa separation of 1 cm between each of members 401-414. Three members408-410 are elongated towards the forehead, and their continuations passin the left-right direction along the orbitofrontal cortex to provideadditional effects in that region, as delineated by segments I-J. Returnpaths 401″-407″ of members 401-407 are attached to the head in the righthemisphere, as delineated by segments D-E. In one embodiment, each ofthe return paths 401″-407″ is separated from one another byapproximately 0.5-1.2 cm. In a preferred embodiment, each of the returnpaths 401″-407″ is separated from one another by approximately 0.8 cm.The return paths 408″-414″ of members 408-414 are situated above thehead at a distance therefrom as delineated by segments M-G. In oneembodiment, each of the return paths 408″-414″ is separated from oneanother by approximately 0.1-0.7 cm. In a preferred embodiment, each ofthe return paths 401″-407″ is separated from one another byapproximately 0.3 cm. In one embodiment, the distance from the head tothe return paths 408″-414″ of members 408-414 is between 4-10 cm. In apreferred embodiment, the distance from the head to the return paths408″-414″ of members 408-414 is approximately 7 cm.

Coil 400 may be composed of any electrically conductive material, suchas metal. Particular embodiments have coils comprising wire made ofcopper, aluminum, or other electrically conductive material. In apreferred embodiment, the coil is made of a double 14 AWG insulatedcopper wire having a total length of 750 cm and winded into windings417, connected in series. In a preferred embodiment, coil elements arecoated by a polyurethane resin type Resinex 4 (Hamchaber VehamkasherLtd., Israel), for additional electrical insulation. In alternativeembodiments, coil elements are coated by other insulating materials,such as PVC, or are sandwiched between layers of insulating materials.It should be readily apparent that the embodiments disclosed herein areexamples only and should not be regarded as limiting. The windings 417are connected to an appropriate cable and connector, which is thenconnected to a stimulator. The stimulator may be any appropriatecommercially available power supply, such as the power suppliesavailable for use with other magnetic coils. In preferred embodiments,the stimulator is one of various models of magnetic stimulators producedby Medtronic, Inc. of Minneapolis, Minn., USA (e.g., MagPro, MagLiteCompact), or power supplies sold with various models of magneticstimulators produced by Magstim Company US, LLC, of New York, N.Y., USA(e.g., Magstim Model 200, Magstim Model 220, Magstim Model 250, BiStim,Magstim Rapid, Magstim QuadroPulse).

The stimulator or power supply (not shown) supplies current through lead416 into one of members 401-414. The stimulating current pulses flowsubstantially in the anterior-posterior direction. At this point,current can take one of two paths—either through contacting returnportion 415 or through an ascending portion 421 extending upwards frombase portion 425 and then through protruding return portion 440. Ifcurrent runs through contacting return portion 415, it runs from baseportion 425 to contacting return portion 415 (which runs substantiallyparallel to members of base portion 425, and is positioned directly onthe skull but at a distance from members 401-414 of base portion 325)through an ascending connector 427 and back down to the level of theskull via descending portion 423. From there, current returns throughlead 418 back into the power supply. If current runs through protrudingreturn portion 440, it runs from ascending portion 421, throughprotruding return portion 440 (which runs substantially parallel tomembers of base portion 425), and back down to the level of the skull ata descending portion 423. From there, current returns through lead 418back into the power supply. In a preferred embodiment, half of themembers run through protruding return portion 440 and half of them runthrough contacting return portion 415. However, the invention is notlimited to this proportion, and any proportion of protruding returnpaths and contacting return paths is possible, so long as each returnpath has current from at least one of the members. Current may besupplied simultaneously to all members, or alternatively, may besupplied sequentially, in a random sequence, or selectively. In anotherembodiment, current is supplied to member 401, and runs through a loopincluding each of the additional members 401-414. It should also bereadily apparent that although the invention has been shown withreference to fourteen members, the invention is not in any way limitedto this number, and any suitable number of members may be used. Inadditional embodiments, a single member may have a return path throughboth protruding return portion 440 and contacting return portion 415.

In the preferred embodiment depicted in FIG. 5, current from each ofmembers 401-407 runs through contacting return portion 415 via pathways401″-407″ while current from members 408-414 runs through ascendingportion 421 and through protruding return portion 440 via pathways408″-414″. Specifically, members 401-407 traverse the pathA-B-C-D-E-F-G-H-A. Members 408-410 traverse the path A-I-J-K-L-M-G-H-A.Members 411-414 traverse the path A-N-L-M-G-H-A. It should be readilyapparent that other combinations and pathways are possible, and arewithin the scope of the present invention.

Protruding return portion 414 is spaced a distance from the skull. Inone embodiment, this distance is in a range of 4-10 cm. In a preferredembodiment, this distance is 7 cm. By placing the return path at adistance from the skull, electrical stimulation of unwanted portions ofthe brain is minimized. However, surface charge accumulation at thesurface of the brain is increased. As such, some of the return paths areplaced on the skull itself, so as to reduce surface charge accumulation.However, these return paths are placed a distance from the site to bestimulated within the brain so as to avoid conflicting signals in thearea of stimulation. In one embodiment, the distance from the centralmembers (such as member 414, for example) to the contacting return pathsis in a range of 7-15 cm. In a preferred embodiment, the distance fromthe central members (such as member 414, for example) to the contactingreturn paths is approximately 8 or 9 cm. Thus, a balance is maintainedbetween the need for reducing surface charge and the conflicting need toavoid electrical stimulation of unwanted portions of the brain.

In one embodiment, a screen may be applied to either of coils 300 or 400to further reduce the magnetic field produced when electricity runsthrough the return portions. The screen is comprised of a material withhigh magnetic permeability, capable of inhibiting or diverting amagnetic field, such as mu metal, iron or steel. Alternatively thescreen is comprised of a metal with high conductivity which can causeelectric currents or charge accumulation that may oppose the effectproduced by the return portions. Any suitable screen or shield capableof inhibiting magnetic fields may be used. The screen may be anysuitable size or shape, including but not limited to sheaths of mu metalsurrounding one, some or all of the members of coil 300 or 400, a flatdisc of metal strategically placed, or an enclosure substantiallyenclosing the return paths.

Reference is now made to FIG. 6, which is a block diagram illustrationof a cooling system 88, in accordance with one embodiment of the presentinvention. Although the embodiment described herein refers to water orother liquids used for cooling, it is envisioned that air cooling may beused. The term “fluid” herein denotes liquid such as water, or gas suchas a mixture of gases and more specifically, air. Cooling system 88 isdesigned for maintaining ambient temperature in the coils duringrepetitive operation. Cooling system 88 includes an external coolingunit 500, a fluid circulator 502, and an internal system 504. Internalsystem 504 is connected to coil 300 or 400. Arrows 506 represent thedirection of cooling.

Reference is now made to FIG. 7, which is a block diagram illustrationof external cooling unit 500. External cooling unit 500 includes acompressor 506, a condenser 508, an expansion valve 510, and acarburetor 512. Compressor 506 is a commercially available compressor(available, for example, from Electrolux, Thailand, Type L57TN). In apreferred embodiment, condenser 508 is made of ⅜ inch diameter pipe, andhas 0.5 horse power, a ventilator with 5-30W engine (EMI, Italy), andcurrent of up to 0.20 A. Expansion valve 510 is made of capillary pipehaving approximately a 0.07 inch diameter and a length of 4 meters.Carburetor 512 is made of a ⅜ diameter spiral pipe having a total lengthof at least 4.7 meters.

Reference is now made to FIG. 8, which is a block diagram illustrationof fluid circulator 502. In the embodiment described herein, fluidcirculator is a water circulator, and includes a water tank 514 and awater pump 516. Water tank 514 is in contact with carburetor 512 ofexternal cooling unit 500. In a preferred embodiment, water tank 514 isa 10 liter iron tank coated by a 1 cm layer of foamed polyurethane.Water pump 516 is in fluid communication with internal system 504, andis configured to deliver cooled water to radiators of internal system504. Water pump 516 is a commercially available water pump available,for example, from Pentax, Italy (Type CM50/01). The nominal workingpressure used is 2 bar. The pressure is regulated by a manual feedbackcock. The excess of water returns to the tank and creates circulation.

Cooling is accomplished as follows. Freon gas is compressed incompressor 506, condensed in condenser 508, and expanded throughexpansion valve 510. The capillary in expansion valve 510 is connectedto carburetor 512, where the gas is evaporated again and returns tocompressor 506. Carburetor 512 is immersed in water tank 514, therebycooling the water. The water is pumped out via water pump 516, andcirculated through radiators of internal system 504. In alternativeembodiments, cooled air is circulated instead of water. In oneembodiment, internal system 504 is a radiator system. Radiators are inthermal conjunction with coil 300 or 400, as will be described ingreater detail hereinbelow with reference to FIG. 9. The fluidcirculation cools the coil during pulse trains and stabilizes itstemperature at mild temperature range. In one embodiment, temperaturesensors are located at or near coil 300 or 400, and information abouttemperature during a procedure can be sent directly to cooling system88. Automatic adjustment of cooling can then be done based on thetemperature information.

Reference is now made to FIG. 9, which is a schematic illustration ofinternal system 504 in contact with coils 300 or 400, in accordance withone embodiment of the present invention. In the embodiment shown herein,internal system 504 includes individual radiator units 518 (shownpartially cut), in close thermal contact and approximate geometricalignment with coils 300 or 400. Each of radiator units 518 arecomprised of two parallel ¼ inch pipes, and between them severalcapillary pipes of 0.07 inch diameter. In a preferred embodiment, thepipes are made of copper and are coated by insulating lacquer (John C.Dolph Company, New Jersey, USA). Radiator units 518 are sandwiched bylayers of a thermal and electrical insulator 520. Coil 300 or 400 isalso sandwiched by layers of insulator 520. In a preferred embodiment,insulator 520 is a semi-flexible polyurethane resin, preferably Resinex4 available from Hamchaber and Hamkasher Ltd., Bat Yam, Israel. In apreferred embodiment, at least two layers of insulator 520 are situatedon either side of coil 300 or 400, and at least one layer of insulator520 is further situated between radiator units 518 and helmet 82. Anadditional layer of biocompatible foam medical tape 522 (for example,Type 9776 available from 3M Center, St. Paul, Minn., USA) attaches theentire system to the head of the subject. The number of radiator units518 depends on the number of members or coil units in the coil. Forexample, for coil 300, six radiator units are used, and for coil 400,seven radiator units are used.

Methods of Operation:

The basic method for operating system 80 of the present inventioninvolves the following steps: First, subjects are fitted with earplugsto lessen any possible adverse effect on hearing. The subject is thenseated on chair 85 with his/her heading resting on rear head support 87.Helmet 82 with coil 300 or 400 and radiator units 518 or with any othersuitable cooling system is positioned over the subject's head over theprefrontal cortex, 5 cm anterior to the hot spot for abductor pollicisbrevis (APB) muscle stimulation. The subject's motor threshold ismeasured by delivering single stimulations to the motor cortex, bygradually increasing the intensity (using the single pulse mode,applying one pulse each time) and recording electrical activity inabductor pollicis brevis using surface electrodes. Threshold is definedas the lowest intensity of stimulation able to produce motor evokedpotentials of at least 50 μV in 5 of 10 trials. After defining the motorthreshold, coil 300 or 400 is positioned on the prefrontal cortex, andthe session is performed at 110% of the motor threshold. Stimulator 86is set to required power, frequency and duration values, as determined.Frequency can range from 1-50 Hz.

Each treatment session includes a predetermined number of trains. Insome embodiments, a train of 1 to 100 pulses is administered. Individualpulses measure from about 50 to 2000 microseconds, preferably in the1000 microsecond range. In a preferred embodiment, the duration of eachtrain is 1 second, with an inter-train interval of 20 seconds.Alternative durations and intervals are possible as well. Treatmentplans can include, for example, an increase in the frequency used ondifferent days. Pulses can vary in frequency as well as number. Certainembodiments use a frequency range of about 1 to 100 Hz.

In a preferred embodiment, each treatment session includes 42 trains.The duration of each train is 1 second and the inter-train interval is20 seconds. Each subject undergoes three treatment sessions, on day 1, 3and 5. On day 1, stimulation is 1 Hz, on day 2, stimulation is 10 Hz,and on day 3, stimulation is 20 Hz.

The basic principles and operation of the system is based on summationof electrical impulses. The general concept of summation is that byproviding several sub-threshold impulses, it is possible to stimulatedeep regions of the brain without unwanted stimulation or excessiveelectrical field applied at surface areas of the brain. In prior artInternational Publication Number WO 02/32504, this concept was appliedspatially by using several coil elements carrying current in a desireddirection, each placed in a different location around the head such thathigh electric field intensity is concentrated in a specific deep brainregion, while maintaining a high ratio of deep brain electrical field tosurface electrical field. This type of spatial summation can be termedone-point spatial summation, since each of the individual elementsstimulates the same focused point.

While one-point spatial summation has been shown to be advantageous,other more specific methods could be useful in further increasing thedepth penetration and specificity of the treatment.

In one embodiment of the present invention, a different type of spatialsummation is contemplated. Rather than focusing on a single point,several points along a neuronal structure can be stimulated, causing anet result depolarization at an even lower electrical field strength.This type of spatial summation can be termed morphological line spatialsummation. The points along the neuron at which the electric field isproduced may or may not be in a straight line configuration. If, forexample, a path of a specific axonal bundle is known, such as forexample the medial forebrain bundle, the coil can be designed in aconfiguration to produce significant electrical fields at several pointsalong the bundle. The configuration of the coil would approximate thepath of the bundle, which can be determined, for example, by a fibertracking diffusion tensor MRI or by other known imaging methods. Thisconfiguration may enable induction of an action potential in the bundle,while minimizing activation of other brain regions. Specifically, thecoil can be activated at an intensity which is sub-threshold and thuswould not induce an action potential at one specific brain region, butsince it is being induced along a specific path, the summation of pointsin space would be enough to induce the action potential in the desiredaxonal bundle.

In another embodiment, each of the various coil members can bestimulated consecutively and not simultaneously, resulting in temporalsummation. Reference is now made to FIG. 10, which is astrength/duration curve for activation of an action potential in themotor cortex and the sensory cortex, according to the data reported byBourland et al. (Bourland J D, Nyenhuis J A, Noe W A, Schaefer J D,Foster K S, and Geddes L A, in Proc. Int. Soc. Magnetic Resonance inMedicine 4^(th) Scientific Meeting, New York, 1996, p 1724). Neuronalactivation threshold depends on both the strength or intensity of theelectric field and the stimulation duration. In addition, the thresholdmay be reduced by applying several pulses with short intervals betweenthem. Thus, it is possible to stimulate an action potential with reducedstimulation intensity by increasing the duration of the stimulation.While increasing the duration of a single pulse might be painful ordetrimental to the surface areas of the brain, summing a series ofindividual pulses over a duration of time could have the desired effect.The coil may be designed in a configuration such that the variousmembers are scattered around a desired region or path, and may bestimulated consecutively so that at each time period only a certainelement or group of elements is activated. This way, a significantelectrical field can be induced at the desired region for all timeperiods, or with short inter-pulse intervals that may still enableactivation, while in the cortical region of the brain, only certainregions will experience a significant field at certain periods, and theintervals between experiences of significant field will be much longer.This can be accomplished by using more than one stimulator, or by usinga configuration of a stimulator which includes several channels forstimulation.

A method of transcranial magnetic stimulation using temporal summationin accordance with one embodiment of the invention is as follows. A coil300 or 400 such as the one described above with reference to FIGS. 4 and5 is placed on the skull. In one embodiment, electrical leads areconnected to one power supply or stimulator with multiple channels. Inanother embodiment, additional leads are separately connected to two ormore power supplies and to at least two members for providing electricalstimulation. Pulses are applied at a lower voltage and/or rate of changeof electric current, so that the field induced at cortical brain regionswill be sub-threshold or around the threshold level, but are applied todifferent members at different times. In one embodiment, differentstimulations are applied at 100 microsecond intervals. In otherembodiments the different pulses are applied at between 10 to 1000microsecond intervals, or even at several milliseconds intervals. In oneembodiment, members are activated in a sequential order. In anotherembodiment, only certain members are activated, or a random pattern isgenerated. In other embodiments, groups of members are activated in acertain order. For example, with reference to FIG. 3A, the followingsequence may be used:

Period 1: members 210-216, 234-240, 256-260

Period 2: members 218-224, 242-248

Period 3: members 226-232, 250-254

In one embodiment, two or more of the various types of summation arecombined. For example, morphological line spatial summation can be usedat a sub-threshold intensity in combination with temporal summation.That is, different parts of an axonal bundle can be targeted selectivelyor sequentially, rather than simultaneously. Alternatively, one coil caninclude members for one-point summation and for morphological linespatial summation. Each of the member types can be simultaneously,sequentially or selectively stimulated.

The system and methods of the present invention described herein may beused to study or treat a neurophysiological condition. A“neurophysiological condition” may be a pathological neurophysiologicalcondition or a neurophysiological disorder, such as, but not limited to:clinical depression, non-clinical depression, dysthemia, bipolardisorder, drug addiction, substance abuse, anxiety disorder, obsessivecompulsive disorder, Parkinson's disease, post-traumatic stressdisorder, addictions such as smoking and alcoholism, autism, and others.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

EXAMPLE

Reference is now made to the following example, which together with theabove descriptions, illustrate the invention in a non limiting fashion.

The biological efficacy of a coil similar to the ones described abovewith reference to FIGS. 4 and 5 was tested, using motor threshold as ameasure of biological effect. It should be noted that although theexperimental coil, a schematic of which is shown in FIG. 11, is used tostimulate the motor cortex, a region which is accessible and measurable,the results can be appropriately compared to a coil designed tostimulate deep regions of the brain (which is more difficult tomeasure). This comparison was made possible by increasing the distanceof the experimental coil from the site of activation (namely the motorcortex). Thus, a measure of the rate of decrease of electric field as afunction of distance was taken at different distances from the skull.These measurements were compared to measurements taken under the sameconditions using a standard figure-8 coil.

A coil 600 was designed to stimulate the right abductor pollicis brevis(APB), as shown in FIG. 11. The coil 600 has 10 members 601-610 splitinto two groups, designated by A-B and G-H in FIG. 11. The averagelength of the members is 11 cm. The only coil elements having radialcurrent components are members 606-610, which are connected to thereturn paths shown in segments C-I and J-F. The length of the radialconnecting elements is approximately 8 cm. The return paths of the otherfive members 601-605 are placed on the head at the contralateralhemisphere (segment D-E). The wires (segments B-C and F-A) connectingmembers 601-605 and return paths 601′-605′ are approximately 9 cm long,on average. Coil 600 was compared to a standard commercial Magstimfigure-8 coil with internal loop diameters of 7 cm.

Subjects were seated with the right forearm and hand supported. Motorevoked potentials of the right APB muscle were recorded usingsilver-silver chloride surface electrodes. Subjects were instructed tomaintain muscle relaxation throughout the study. EMG amplitude wasamplified using a conventional EMG machine (Counterpoint, DantecElectronics, Skovlunde, Denmark) with band-pass between 10 and 2000 Hz.The signal was digitized at a frequency of 5 kHz and fed into alaboratory computer.

A Magstim Super Rapid stimulator (The Magstim Company New York, N.Y.)which produces a bi-phasic pulse, coupled with either the figure-8 coilor the H-coil, was used. Preliminary studies showed the H-coil to have aloudness level of 122 dB when activated, similar to coils 300 and 400described above in accordance with preferred embodiments of the presentinvention. Subjects were fitted with foam ear plugs to attenuate thesound.

Coil 600 was placed on the scalp over the left motor cortex. Theintersection of the figure-8 coil was placed tangentially to the scalpwith the handle pointing backward and laterally at a 45 degree angleaway from the midline. Coils were held in a stable coil holder whichcould be adjusted at different heights above the “hot spot” on thescalp. Resting motor threshold was determined for each coil at differentdistances above the scalp, at increments of 0.5 cm.

Reference is now made to FIG. 12, which is a graphical illustration ofthe results of the example described above. The graph shows thepercentage of stimulator output needed to reach resting motor thresholdas a function of distance of the coil from the “hot spot” on the skullfor both coil 600 and the standard figure-8 coil. As shown in FIG. 12,the efficacy of coil 600 at large distances from the scalp wassignificantly greater than for the figure-8 coil. When using maximalstimulation power output, the figure-8 coil can be effective up to 2 cmaway from the coil, while coil 600 can be effective at 5.5 cm away fromthe coil. Moreover, the rate of decay of effectiveness as a function ofthe distance from the coil is much slower in coil 600 relative to thefigure-8 coil.

1. A coil for magnetic stimulation of a target area, the coilpositionable on a body part, the coil comprising: a base portioncomprising at least one member for providing electrical current flow ina direction tangential to the target area, said base portion positionedat a first level with respect to the target area; a protruding returnportion for carrying returning current in a direction opposite thetarget area, said protruding return portion in electrical communicationwith said at least one member and positioned at a second level withrespect to the target area, the second level located at a distance abovethe first level; and a contacting return portion for carrying returningcurrent in a direction opposite the target area, said contacting returnportion in electrical communication with said at least one member andpositioned substantially in the first level and spaced at a distancefrom the target area.
 2. The coil of claim 1, wherein said at least onemember includes multiple members.
 3. The coil of claim 1, wherein saidat least one member includes 10 members.
 4. The coil of claim 1, whereinsaid at least one member includes 14 members.
 5. The coil of claim 2,wherein a portion of said multiple members is in electricalcommunication with said protruding return portion and a portion of saidmultiple members is in electrical communication with said contactingreturn portion.
 6. The coil of claim 1, wherein said at least one memberis positioned in a lateral-medial direction.
 7. The coil of claim 1,wherein said at least one member is positioned in an anterior-posteriordirection.
 8. The coil of claim 2, wherein said multiple members areparallel to one another.
 9. The coil of claim 1, wherein said firstlevel is on the skull.
 10. The coil of claim 1, wherein said distance ofsaid second level above said first level is 4-10 cm.
 11. The coil ofclaim 1, wherein said distance of said second level above said firstlevel is 7 cm.
 12. The coil of claim 1, wherein said distance of saidcontacting return portion from said target area is 7-10 cm.
 13. The coilof claim 1, wherein said base portion comprises an arch configurationwhich is complementary to the body part.
 14. The coil of claim 1,wherein the body part is a head and the target area is a portion of abrain.
 15. The coil of claim 15, wherein said portion of a brain is atleast 3 cm deep.
 16. A system for transcranial magnetic stimulation, thesystem comprising: a helmet for placement on a head of a subject, thehelmet comprising at least one coil for magnetic stimulation; a rigidcover portion; and a flexible cover portion; a positioning portioncomprising a stand and an adjustable arm, said adjustable arm attachedto said rigid cover portion; a stimulator in electrical communicationwith said at least one coil; and a cooling system comprising an externalunit and an internal system, said internal system in thermal proximityand approximate geometric alignment with at least a portion of said atleast one coil.
 17. The system of claim 17, wherein said at least onecoil comprises: a base portion comprising at least one member forproviding electrical current flow in a direction tangential to a targetarea, said base portion positioned at a first level with respect to thetarget area; a protruding return portion for carrying returning currentin a direction opposite the target area, said protruding return portionin electrical communication with said at least one member and positionedat a second level with respect to the target area, the second levellocated at a distance above the first level; and a contacting returnportion for carrying returning current in a direction opposite thetarget area, said contacting return portion in electrical communicationwith said at least one member and positioned substantially in the firstlevel and spaced at a distance from the target area.
 18. The system ofclaim 17, wherein said positionable portion further comprises a chairand a rear head support.
 19. The system of claim 17, further comprisingan additional stimulator, in electrical communication with said at leastone coil.
 20. The system of claim 17, wherein said internal system isseparated from said coils by an insulator.
 21. The system of claim 20,wherein said insulator is a polyurethane resin.
 22. A method forstimulation of a deep brain region, the method comprising: providing acoil having a base portion for delivering current to the deep brainregion, the base portion positionable on a skull; a protruding returnportion for carrying returning current and positionable above the skull;and a contacting return portion for carrying returning current andpositionable on the skull but at a distance from the base portion;placing said coil on the skull of a subject, such that said base portionand said contacting return portion are in contact with the skull andsaid protruding return portion is located at a distance above the skull;and activating said coil to stimulate the deep brain region.
 23. Themethod of claim 22, wherein said activating comprises providingelectrical impulses to said coils.
 24. The method of claim 23, whereinsaid providing comprises simultaneously providing electrical impulses toindividual members of said coil.
 25. The method of claim 23, whereinsaid providing comprises sequentially providing electrical impulses toindividual members of said coil.
 26. A method of activating a neuronalstructure, the method comprising: providing a coil for delivery ofelectrical impulses to a target area, the coil including individualmembers designed to carry current in predetermined directions; andactivating said individual members non-simultaneously.
 27. The method ofclaim 26, wherein said predetermined directions are a same direction foreach of said individual members.
 28. The method of claim 26, whereinsaid predetermined directions are a different direction for each of saidindividual members, and wherein each of said predetermined directionsforms a path designed to mimic a neuronal structure.
 29. The method ofclaim 26, wherein said activating comprises sequentially activating eachof said individual members.
 30. The method of claim 26, wherein saidactivating comprises randomly activating each of said individualmembers.
 31. The method of claim 26, wherein said activating comprisesselectively activating some of said individual members.